Oil-in-water emulsions generally comprise an aqueous phase having suspended therein discrete oil droplets (particles) surrounded by a layer of at least one water soluble surfactant. Emulsion stability is largely determined by particle size; oil-in-water-emulsions having particle sizes that exceed 1 μm in diameter tend to be less stable and undergo creaming, coagulation and phase separation upon storage. Therefore, for most applications it is desirable to reduce particle size which generally results in significant increases in aqueous phase surfactant concentration. The smaller the particle size, the greater the combined particle surface area resulting in a need for more surfactant in the aqueous phase, thus more free surfactant in solution.
Oil-in-water emulsions have a wide rage of ophthalmic applications including preparing solutions useful for treating storing and cleaning contact lenses, providing demulcents and lubricants and acting as carriers for therapeutic compositions. Ophthalmic emulsions may be specialized or multi-purpose solutions. Examples of specialized ophthalmic solutions include treatments for keratoconjunctivitis sicca (dry eye). Dry eye results from evaporation of naturally occurring water from the eye surface. Dry eye treatment compositions generally comprise oil-in-water emulsions that restore the eye's natural aqueous layer and provide an oil layer over the newly added aqueous layer to prevent further evaporation. In other embodiments dry eye treatment compositions are emulsions that also contain hydrophobic therapeutic agents such as cyclosporine and/or a variety of demulcents such as carboxymethyl cellulose, hydroxyproyl cellulose, hyaluronic acid, polyvinyl alcohol, polysorbates, providone and other. Still other dry eye specialty ophthalmic solutions compositions may include at lease one therapeutic agent such as cyclosporine A.
However, all ophthalmic compositions comprising an oil-in-water emulsion used directly in the eye, whether as a dedication artificial tear or dry eye therapeutic, achieve maximum efficacy when the oil phase spreads evenly and freely over the eye surface. Moreover, ophthalmic emulsions should be relatively stable on storing to permit convenient frequent application to the eye. However, many oil-in-water emulsions contain excessive amounts of free hydrophilic surfactant. The free hydrophilic surfactant can wash away the tear film's natural lipid component and damage the mucin layer covering the cornea or conjunctiva thus exacerbating dry eye. Therefore, oil-in-water emulsion having a small particle size (average less than 1 μm in diameter) that contain non-irritating amounts of eye-damaging free hydrophilic surfactant in the aqueous phase are desirable